Alterations of mesenchymal and endothelial cells in inflammatory bowel diseases.

The pathogenesis of complex chronic diseases like inflammatory bowel disease (IBD) can no longer be viewed as a one-way street in which classical immune cells have exclusive control over the initiation, duration and outcome of the disease. There is enough experimental evidence to demonstrate that nonimmune cells, among which are mucosal mesenchymal and endothelial cells, also play a decisive role by interacting with immune cells and establishing a two-way reciprocal exchange of signals and responses that dictate the ultimate outcome of inflammation. Smooth muscle cells and fibroblasts/myofibroblasts display a variety of immune functions and modulate the activity and survival of T-cells. Mucosal microvascular cells, through the expression of adhesion molecules and secretion of chemokines, regulate the quantity and quality of leukocytes transmigrating into the interstitial space. A number of receptor-ligand pairs are expressed by immune and nonimmune cells that control their functional interplay, but the CD40/CD40 ligand system may be the most effective because CD40 is expressed by activated muscle and endothelial cells, while the CD40 ligand is expressed by activated T-cells and platelets. The activation of this system in IBD can lead to the establishment of a continuous cycle of nonimmune cell-dependent, antigen-independent interactions that perpetuates gut inflammation.